MFAP5_HUMAN
ID MFAP5_HUMAN Reviewed; 173 AA.
AC Q13361; B0AZL6; D3DUV1; Q7Z490;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Microfibrillar-associated protein 5;
DE Short=MFAP-5;
DE AltName: Full=MP25;
DE AltName: Full=Microfibril-associated glycoprotein 2;
DE Short=MAGP-2;
DE Flags: Precursor;
GN Name=MFAP5; Synonyms=MAGP2;
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] (ISOFORM 1), AND FUNCTION.
RX PubMed=8557636; DOI=10.1074/jbc.271.2.1096;
RA Gibson M.A., Hatzinikolas G., Kumaratilake J.S., Sandberg L.B.,
RA Nicholl J.K., Sutherland G.R., Cleary E.G.;
RT "Further characterization of proteins associated with elastic fiber
RT microfibrils including the molecular cloning of MAGP-2 (MP25).";
RL J. Biol. Chem. 271:1096-1103(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=9792630; DOI=10.1074/jbc.273.45.29309;
RA Hatzinikolas G., Gibson M.A.;
RT "The exon structure of the human MAGP-2 gene. Similarity with the MAGP-1
RT gene is confined to two exons encoding a cysteine-rich region.";
RL J. Biol. Chem. 273:29309-29314(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Li H., Cao L., Zhou G., Shen C., Zhong G., Yu R., Lin L., Yang S.;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Tongue;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
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 [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-79.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [9]
RP GLYCOSYLATION AT THR-54, STRUCTURE OF CARBOHYDRATES, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=22171320; DOI=10.1074/mcp.m111.013649;
RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT "Human urinary glycoproteomics; attachment site specific analysis of N- and
RT O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 11:1-17(2012).
RN [10]
RP INVOLVEMENT IN AAT9, VARIANT AAT9 LEU-21, AND CHARACTERIZATION OF VARIANT
RP AAT9 LEU-21.
RX PubMed=25434006; DOI=10.1016/j.ajhg.2014.10.018;
RA Barbier M., Gross M.S., Aubart M., Hanna N., Kessler K., Guo D.C.,
RA Tosolini L., Ho-Tin-Noe B., Regalado E., Varret M., Abifadel M.,
RA Milleron O., Odent S., Dupuis-Girod S., Faivre L., Edouard T., Dulac Y.,
RA Busa T., Gouya L., Milewicz D.M., Jondeau G., Boileau C.;
RT "MFAP5 loss-of-function mutations underscore the involvement of matrix
RT alteration in the pathogenesis of familial thoracic aortic aneurysms and
RT dissections.";
RL Am. J. Hum. Genet. 95:736-743(2014).
RN [11]
RP VARIANT [LARGE SCALE ANALYSIS] ASP-61.
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: May play a role in hematopoiesis. In the cardiovascular
CC system, could regulate growth factors or participate in cell signaling
CC in maintaining large vessel integrity (By similarity). Component of the
CC elastin-associated microfibrils (PubMed:8557636).
CC {ECO:0000250|UniProtKB:Q9QZJ6, ECO:0000269|PubMed:8557636}.
CC -!- SUBUNIT: Interacts with TGFB2. Interacts with BMP2. Interacts with FBN1
CC (via N-terminal domain) and FBN2. {ECO:0000250|UniProtKB:Q28022,
CC ECO:0000250|UniProtKB:Q9QZJ6}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13361-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13361-2; Sequence=VSP_056618;
CC -!- PTM: Forms intermolecular disulfide bonds either with other MAGP-2
CC molecules or with other components of the microfibrils.
CC -!- PTM: N- and O-glycosylated. O-glycosylated with core 1 or possibly core
CC 8 glycans. O-glycan heterogeneity at Thr-54: HexHexNAc (major) and
CC HexHexNAc + sulfate (minor). {ECO:0000269|PubMed:19159218,
CC ECO:0000269|PubMed:22171320}.
CC -!- DISEASE: Aortic aneurysm, familial thoracic 9 (AAT9) [MIM:616166]: A
CC disease characterized by permanent dilation of the thoracic aorta
CC usually due to degenerative changes in the aortic wall. It is primarily
CC associated with a characteristic histologic appearance known as 'medial
CC necrosis' or 'Erdheim cystic medial necrosis' in which there is
CC degeneration and fragmentation of elastic fibers, loss of smooth muscle
CC cells, and an accumulation of basophilic ground substance.
CC {ECO:0000269|PubMed:25434006}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the MFAP family. {ECO:0000305}.
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DR EMBL; U37283; AAA96752.1; -; mRNA.
DR EMBL; AF084927; AAC83942.1; -; Genomic_DNA.
DR EMBL; AF084919; AAC83942.1; JOINED; Genomic_DNA.
DR EMBL; AF084920; AAC83942.1; JOINED; Genomic_DNA.
DR EMBL; AF084921; AAC83942.1; JOINED; Genomic_DNA.
DR EMBL; AF084922; AAC83942.1; JOINED; Genomic_DNA.
DR EMBL; AF084923; AAC83942.1; JOINED; Genomic_DNA.
DR EMBL; AF084924; AAC83942.1; JOINED; Genomic_DNA.
DR EMBL; AF084925; AAC83942.1; JOINED; Genomic_DNA.
DR EMBL; AF084926; AAC83942.1; JOINED; Genomic_DNA.
DR EMBL; AY339060; AAQ18021.1; -; mRNA.
DR EMBL; AK299475; BAG61439.1; -; mRNA.
DR EMBL; AK315807; BAF98698.1; -; mRNA.
DR EMBL; AC092184; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092490; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471116; EAW88613.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88614.1; -; Genomic_DNA.
DR EMBL; BC005901; AAH05901.1; -; mRNA.
DR CCDS; CCDS73437.1; -. [Q13361-2]
DR CCDS; CCDS8595.1; -. [Q13361-1]
DR RefSeq; NP_001284638.1; NM_001297709.1. [Q13361-2]
DR RefSeq; NP_003471.1; NM_003480.3. [Q13361-1]
DR AlphaFoldDB; Q13361; -.
DR BioGRID; 113750; 68.
DR STRING; 9606.ENSP00000352455; -.
DR GlyConnect; 752; 4 N-Linked glycans (1 site), 3 O-Linked glycans (1 site).
DR GlyGen; Q13361; 3 sites, 3 N-linked glycans (1 site), 3 O-linked glycans (2 sites).
DR iPTMnet; Q13361; -.
DR PhosphoSitePlus; Q13361; -.
DR BioMuta; MFAP5; -.
DR DMDM; 2498553; -.
DR jPOST; Q13361; -.
DR MassIVE; Q13361; -.
DR PaxDb; Q13361; -.
DR PeptideAtlas; Q13361; -.
DR PRIDE; Q13361; -.
DR ProteomicsDB; 59344; -. [Q13361-1]
DR ProteomicsDB; 69162; -.
DR Antibodypedia; 2040; 223 antibodies from 32 providers.
DR DNASU; 8076; -.
DR Ensembl; ENST00000359478.7; ENSP00000352455.2; ENSG00000197614.11. [Q13361-1]
DR Ensembl; ENST00000396549.6; ENSP00000379798.2; ENSG00000197614.11. [Q13361-2]
DR Ensembl; ENST00000540087.5; ENSP00000440496.1; ENSG00000197614.11. [Q13361-2]
DR GeneID; 8076; -.
DR KEGG; hsa:8076; -.
DR MANE-Select; ENST00000359478.7; ENSP00000352455.2; NM_003480.4; NP_003471.1.
DR UCSC; uc001qus.3; human. [Q13361-1]
DR CTD; 8076; -.
DR DisGeNET; 8076; -.
DR GeneCards; MFAP5; -.
DR HGNC; HGNC:29673; MFAP5.
DR HPA; ENSG00000197614; Tissue enhanced (endometrium).
DR MalaCards; MFAP5; -.
DR MIM; 601103; gene.
DR MIM; 616166; phenotype.
DR neXtProt; NX_Q13361; -.
DR OpenTargets; ENSG00000197614; -.
DR Orphanet; 91387; Familial thoracic aortic aneurysm and aortic dissection.
DR PharmGKB; PA134915148; -.
DR VEuPathDB; HostDB:ENSG00000197614; -.
DR eggNOG; ENOG502S4DY; Eukaryota.
DR GeneTree; ENSGT00390000017736; -.
DR InParanoid; Q13361; -.
DR OMA; LXCRDEK; -.
DR OrthoDB; 288325at2759; -.
DR PhylomeDB; Q13361; -.
DR TreeFam; TF333418; -.
DR PathwayCommons; Q13361; -.
DR Reactome; R-HSA-1566948; Elastic fibre formation.
DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres.
DR SignaLink; Q13361; -.
DR BioGRID-ORCS; 8076; 12 hits in 1060 CRISPR screens.
DR ChiTaRS; MFAP5; human.
DR GeneWiki; MFAP5; -.
DR GenomeRNAi; 8076; -.
DR Pharos; Q13361; Tbio.
DR PRO; PR:Q13361; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q13361; protein.
DR Bgee; ENSG00000197614; Expressed in synovial joint and 163 other tissues.
DR ExpressionAtlas; Q13361; baseline and differential.
DR Genevisible; Q13361; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0001527; C:microfibril; ISS:UniProtKB.
DR GO; GO:0005201; F:extracellular matrix structural constituent; TAS:ProtInc.
DR GO; GO:0060216; P:definitive hemopoiesis; ISS:UniProtKB.
DR GO; GO:0048048; P:embryonic eye morphogenesis; IBA:GO_Central.
DR GO; GO:0097435; P:supramolecular fiber organization; IEA:Ensembl.
DR InterPro; IPR008673; MAGP.
DR PANTHER; PTHR16485; PTHR16485; 1.
DR Pfam; PF05507; MAGP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Aortic aneurysm; Disease variant; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..173
FT /note="Microfibrillar-associated protein 5"
FT /id="PRO_0000018685"
FT MOTIF 30..32
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT CARBOHYD 54
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:22171320"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT VAR_SEQ 73..82
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_056618"
FT VARIANT 21
FT /note="W -> L (in AAT9; expression of the mutant protein is
FT significantly decreased; dbSNP:rs724159961)"
FT /evidence="ECO:0000269|PubMed:25434006"
FT /id="VAR_072688"
FT VARIANT 61
FT /note="V -> D (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036430"
SQ SEQUENCE 173 AA; 19612 MW; 70CE35B303C710A0 CRC64;
MSLLGPKVLL FLAAFIITSD WIPLGVNSQR GDDVTQATPE TFTEDPNLVN DPATDETVLA
VLADIAPSTD DLASLSEKNT TAECWDEKFT CTRLYSVHRP VKQCIHQLCF TSLRRMYIVN
KEICSRLVCK EHEAMKDELC RQMAGLPPRR LRRSNYFRLP PCENVDLQRP NGL
