MCFD2_HUMAN
ID MCFD2_HUMAN Reviewed; 146 AA.
AC Q8NI22; A8K7W2; D6W5A9; E9PD95; Q53SS3; Q68D61; Q8N3M5;
DT 21-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Multiple coagulation factor deficiency protein 2;
DE AltName: Full=Neural stem cell-derived neuronal survival protein;
DE Flags: Precursor;
GN Name=MCFD2; Synonyms=SDNSF;
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).
RC TISSUE=Heart;
RA Toda H., Tashiro K., Takahashi J., Hashimoto N., Nakano I., Kobuke K.,
RA Tsuji M., Honjo T.;
RT "Isolation and characterization of SDNSF, a novel secretory molecule with
RT neuronal survival effect, from adult rat hippocampal stem cells.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, INTERACTION
RP WITH LMAN1, FUNCTION, AND VARIANTS F5F8D2 GLU-129 AND THR-136.
RX PubMed=12717434; DOI=10.1038/ng1153;
RA Zhang B., Cunningham M.A., Nichols W.C., Bernat J.A., Seligsohn U.,
RA Pipe S.W., McVey J.H., Schulte-Overberg U., de Bosch N.B., Ruiz-Saez A.,
RA White G.C., Tuddenham E.G., Kaufman R.J., Ginsburg D.;
RT "Bleeding due to disruption of a cargo-specific ER-to-Golgi transport
RT complex.";
RL Nat. Genet. 34:220-225(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Synovium;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
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] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Skin;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [11]
RP STRUCTURE BY NMR OF 27-146, DOMAIN, CHARACTERIZATION OF VARIANTS F5F8D2
RP GLU-129 AND THR-136, AND CALCIUM-BINDING.
RX PubMed=18590741; DOI=10.1016/j.jmb.2008.06.042;
RA Guy J.E., Wigren E., Svaerd M., Haerd T., Lindqvist Y.;
RT "New insights into multiple coagulation factor deficiency from the solution
RT structure of human MCFD2.";
RL J. Mol. Biol. 381:941-955(2008).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 58-146 IN COMPLEX WITH LMAN1, AND
RP SUBUNIT.
RX PubMed=20138881; DOI=10.1016/j.febslet.2010.02.009;
RA Wigren E., Bourhis J.M., Kursula I., Guy J.E., Lindqvist Y.;
RT "Crystal structure of the LMAN1-CRD/MCFD2 transport receptor complex
RT provides insight into combined deficiency of factor V and factor VIII.";
RL FEBS Lett. 584:878-882(2010).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 27-146 IN COMPLEX WITH LMAN1,
RP SUBUNIT, AND CALCIUM-BINDING SITES.
RX PubMed=20142513; DOI=10.1073/pnas.0908526107;
RA Nishio M., Kamiya Y., Mizushima T., Wakatsuki S., Sasakawa H., Yamamoto K.,
RA Uchiyama S., Noda M., McKay A.R., Fukui K., Hauri H.P., Kato K.;
RT "Structural basis for the cooperative interplay between the two causative
RT gene products of combined factor V and factor VIII deficiency.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:4034-4039(2010).
RN [14]
RP VARIANT F5F8D2 ASN-135.
RX PubMed=18685427; DOI=10.1097/mbc.0b013e3283061103;
RA Ivaskevicius V., Windyga J., Baran B., Bykowska K., Daugela L., Watzka M.,
RA Seifried E., Oldenburg J.;
RT "The first case of combined coagulation factor V and coagulation factor
RT VIII deficiency in Poland due to a novel p.Tyr135Asn missense mutation in
RT the MCFD2 gene.";
RL Blood Coagul. Fibrinolysis 19:531-534(2008).
RN [15]
RP VARIANT F5F8D2 HIS-81.
RX PubMed=20491958; DOI=10.1111/j.1365-2516.2010.02268.x;
RA Abdallah H.E., Gouider E., Amor M.B., Jlizi A., Meddeb B., Elgaaied A.;
RT "Molecular analysis in two Tunisian families with combined factor V and
RT factor VIII deficiency.";
RL Haemophilia 16:801-804(2010).
CC -!- FUNCTION: The MCFD2-LMAN1 complex forms a specific cargo receptor for
CC the ER-to-Golgi transport of selected proteins. Plays a role in the
CC secretion of coagulation factors. {ECO:0000269|PubMed:12717434}.
CC -!- SUBUNIT: Interacts in a calcium-dependent manner with LMAN1.
CC {ECO:0000269|PubMed:12717434, ECO:0000269|PubMed:20138881,
CC ECO:0000269|PubMed:20142513}.
CC -!- INTERACTION:
CC Q8NI22; P06307: CCK; NbExp=3; IntAct=EBI-2689785, EBI-6624398;
CC Q8NI22; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-2689785, EBI-11522780;
CC Q8NI22; Q01638-2: IL1RL1; NbExp=3; IntAct=EBI-2689785, EBI-12838366;
CC Q8NI22; P13473-2: LAMP2; NbExp=3; IntAct=EBI-2689785, EBI-21591415;
CC Q8NI22; P49257: LMAN1; NbExp=12; IntAct=EBI-2689785, EBI-1057738;
CC Q8NI22; Q15077: P2RY6; NbExp=3; IntAct=EBI-2689785, EBI-10235794;
CC Q8NI22; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-2689785, EBI-8652812;
CC Q8NI22; O00767: SCD; NbExp=3; IntAct=EBI-2689785, EBI-2684237;
CC Q8NI22; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-2689785, EBI-2623095;
CC Q8NI22; P78382: SLC35A1; NbExp=3; IntAct=EBI-2689785, EBI-12870360;
CC Q8NI22; Q8N2H4: SYS1; NbExp=3; IntAct=EBI-2689785, EBI-13075176;
CC Q8NI22; Q9TU32: LMAN1; Xeno; NbExp=2; IntAct=EBI-2689785, EBI-25399342;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum-Golgi intermediate
CC compartment {ECO:0000269|PubMed:12717434}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:12717434}. Golgi apparatus
CC {ECO:0000269|PubMed:12717434}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8NI22-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NI22-2; Sequence=VSP_043815;
CC Name=3;
CC IsoId=Q8NI22-3; Sequence=VSP_043814;
CC -!- DOMAIN: Essentially unstructured in the absence of calcium ions.
CC Requires calcium ions for folding. {ECO:0000269|PubMed:18590741}.
CC -!- DISEASE: Factor V and factor VIII combined deficiency 2 (F5F8D2)
CC [MIM:613625]: A blood coagulation disorder characterized by bleeding
CC symptoms similar to those in hemophilia or parahemophilia, that are
CC caused by single deficiency of FV or FVIII, respectively. The most
CC common symptoms are epistaxis, menorrhagia, and excessive bleeding
CC during or after trauma. Plasma levels of coagulation factors V and VIII
CC are in the range of 5 to 30% of normal. {ECO:0000269|PubMed:12717434,
CC ECO:0000269|PubMed:18590741, ECO:0000269|PubMed:18685427,
CC ECO:0000269|PubMed:20491958}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD38756.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF475284; AAM28465.1; -; mRNA.
DR EMBL; AF537214; AAP23162.1; -; mRNA.
DR EMBL; AK292127; BAF84816.1; -; mRNA.
DR EMBL; AL833900; CAD38756.1; ALT_INIT; mRNA.
DR EMBL; CR749562; CAH18359.1; -; mRNA.
DR EMBL; AC016722; AAY15013.1; -; Genomic_DNA.
DR EMBL; AC093732; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAX00230.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00231.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00232.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00233.1; -; Genomic_DNA.
DR EMBL; BC037845; AAH37845.1; -; mRNA.
DR EMBL; BC040357; AAH40357.1; -; mRNA.
DR CCDS; CCDS33192.1; -. [Q8NI22-1]
DR CCDS; CCDS54354.1; -. [Q8NI22-2]
DR CCDS; CCDS54355.1; -. [Q8NI22-3]
DR PIR; JS0027; JS0027.
DR RefSeq; NP_001164977.1; NM_001171506.2. [Q8NI22-1]
DR RefSeq; NP_001164978.1; NM_001171507.2. [Q8NI22-1]
DR RefSeq; NP_001164979.1; NM_001171508.2. [Q8NI22-1]
DR RefSeq; NP_001164980.1; NM_001171509.2. [Q8NI22-2]
DR RefSeq; NP_001164981.1; NM_001171510.2. [Q8NI22-2]
DR RefSeq; NP_001164982.1; NM_001171511.2. [Q8NI22-3]
DR RefSeq; NP_644808.1; NM_139279.5. [Q8NI22-1]
DR PDB; 2VRG; NMR; -; A=27-146.
DR PDB; 3A4U; X-ray; 1.84 A; B=27-146.
DR PDB; 3LCP; X-ray; 2.45 A; C/D=58-146.
DR PDB; 3WHT; X-ray; 1.80 A; B=67-146.
DR PDB; 3WHU; X-ray; 2.60 A; B=67-146.
DR PDB; 3WNX; X-ray; 2.75 A; B=67-146.
DR PDB; 4YGB; X-ray; 1.60 A; B/D=67-146.
DR PDB; 4YGC; X-ray; 2.40 A; B/D/F/H=67-146.
DR PDB; 4YGD; X-ray; 2.51 A; B/D/F/H=67-146.
DR PDB; 4YGE; X-ray; 3.05 A; B/D/F=27-146.
DR PDBsum; 2VRG; -.
DR PDBsum; 3A4U; -.
DR PDBsum; 3LCP; -.
DR PDBsum; 3WHT; -.
DR PDBsum; 3WHU; -.
DR PDBsum; 3WNX; -.
DR PDBsum; 4YGB; -.
DR PDBsum; 4YGC; -.
DR PDBsum; 4YGD; -.
DR PDBsum; 4YGE; -.
DR AlphaFoldDB; Q8NI22; -.
DR BMRB; Q8NI22; -.
DR SMR; Q8NI22; -.
DR BioGRID; 124712; 74.
DR DIP; DIP-56233N; -.
DR IntAct; Q8NI22; 15.
DR MINT; Q8NI22; -.
DR STRING; 9606.ENSP00000386651; -.
DR DrugBank; DB00025; Antihemophilic factor, human recombinant.
DR DrugBank; DB13998; Lonoctocog alfa.
DR DrugBank; DB13999; Moroctocog alfa.
DR TCDB; 9.B.417.1.1; the mcfd2/lman1 complex receptor (mlm-cr) family.
DR GlyGen; Q8NI22; 2 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; Q8NI22; -.
DR PhosphoSitePlus; Q8NI22; -.
DR BioMuta; MCFD2; -.
DR DMDM; 49036425; -.
DR EPD; Q8NI22; -.
DR jPOST; Q8NI22; -.
DR MassIVE; Q8NI22; -.
DR MaxQB; Q8NI22; -.
DR PaxDb; Q8NI22; -.
DR PeptideAtlas; Q8NI22; -.
DR PRIDE; Q8NI22; -.
DR ProteomicsDB; 73813; -. [Q8NI22-1]
DR ProteomicsDB; 73814; -. [Q8NI22-2]
DR ProteomicsDB; 73815; -. [Q8NI22-3]
DR TopDownProteomics; Q8NI22-1; -. [Q8NI22-1]
DR Antibodypedia; 29996; 182 antibodies from 29 providers.
DR DNASU; 90411; -.
DR Ensembl; ENST00000319466.9; ENSP00000317271.4; ENSG00000180398.13. [Q8NI22-1]
DR Ensembl; ENST00000409105.5; ENSP00000386651.1; ENSG00000180398.13. [Q8NI22-1]
DR Ensembl; ENST00000409147.1; ENSP00000387082.1; ENSG00000180398.13. [Q8NI22-2]
DR Ensembl; ENST00000409207.5; ENSP00000386386.1; ENSG00000180398.13. [Q8NI22-1]
DR Ensembl; ENST00000409218.5; ENSP00000386261.1; ENSG00000180398.13. [Q8NI22-1]
DR Ensembl; ENST00000409800.5; ENSP00000387202.1; ENSG00000180398.13. [Q8NI22-2]
DR Ensembl; ENST00000409913.5; ENSP00000386941.1; ENSG00000180398.13. [Q8NI22-2]
DR Ensembl; ENST00000409973.5; ENSP00000386279.1; ENSG00000180398.13. [Q8NI22-1]
DR Ensembl; ENST00000412438.5; ENSP00000402717.1; ENSG00000180398.13. [Q8NI22-1]
DR Ensembl; ENST00000444761.6; ENSP00000394647.2; ENSG00000180398.13. [Q8NI22-3]
DR GeneID; 90411; -.
DR KEGG; hsa:90411; -.
DR MANE-Select; ENST00000319466.9; ENSP00000317271.4; NM_139279.6; NP_644808.1.
DR UCSC; uc002rvk.4; human. [Q8NI22-1]
DR CTD; 90411; -.
DR DisGeNET; 90411; -.
DR GeneCards; MCFD2; -.
DR HGNC; HGNC:18451; MCFD2.
DR HPA; ENSG00000180398; Low tissue specificity.
DR MalaCards; MCFD2; -.
DR MIM; 607788; gene.
DR MIM; 613625; phenotype.
DR neXtProt; NX_Q8NI22; -.
DR OpenTargets; ENSG00000180398; -.
DR Orphanet; 35909; Combined deficiency of factor V and factor VIII.
DR PharmGKB; PA134925788; -.
DR VEuPathDB; HostDB:ENSG00000180398; -.
DR eggNOG; KOG4065; Eukaryota.
DR GeneTree; ENSGT00940000154141; -.
DR HOGENOM; CLU_100744_2_0_1; -.
DR InParanoid; Q8NI22; -.
DR OMA; NSERDDY; -.
DR OrthoDB; 1601131at2759; -.
DR PhylomeDB; Q8NI22; -.
DR TreeFam; TF315801; -.
DR PathwayCommons; Q8NI22; -.
DR Reactome; R-HSA-204005; COPII-mediated vesicle transport.
DR Reactome; R-HSA-5694530; Cargo concentration in the ER.
DR Reactome; R-HSA-948021; Transport to the Golgi and subsequent modification.
DR SignaLink; Q8NI22; -.
DR BioGRID-ORCS; 90411; 8 hits in 1071 CRISPR screens.
DR ChiTaRS; MCFD2; human.
DR EvolutionaryTrace; Q8NI22; -.
DR GeneWiki; MCFD2; -.
DR GenomeRNAi; 90411; -.
DR Pharos; Q8NI22; Tbio.
DR PRO; PR:Q8NI22; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8NI22; protein.
DR Bgee; ENSG00000180398; Expressed in parotid gland and 216 other tissues.
DR ExpressionAtlas; Q8NI22; baseline and differential.
DR Genevisible; Q8NI22; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; TAS:Reactome.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016192; P:vesicle-mediated transport; IEA:UniProtKB-KW.
DR DisProt; DP01637; -.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF13499; EF-hand_7; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Disease variant;
KW Endoplasmic reticulum; ER-Golgi transport; Golgi apparatus; Metal-binding;
KW Phosphoprotein; Protein transport; Reference proteome; Repeat; Signal;
KW Transport.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..146
FT /note="Multiple coagulation factor deficiency protein 2"
FT /id="PRO_0000004159"
FT DOMAIN 68..103
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 116..146
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 81
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 83
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 85
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 92
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 129
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 131
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 133
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 135
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 140
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K5B3"
FT VAR_SEQ 1..52
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_043815"
FT VAR_SEQ 1..50
FT /note="MTMRSLLRTPFLCGLLWAFCAPGARAEEPAASFSQPGSMGLDKNTVHDQE
FT -> MLSVCSCRTSSGMRSQWPSARQRSSSLSTFR (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_043814"
FT VARIANT 81
FT /note="D -> H (in F5F8D2; dbSNP:rs78289603)"
FT /evidence="ECO:0000269|PubMed:20491958"
FT /id="VAR_072245"
FT VARIANT 129
FT /note="D -> E (in F5F8D2; interferes with protein folding;
FT dbSNP:rs137852913)"
FT /evidence="ECO:0000269|PubMed:12717434,
FT ECO:0000269|PubMed:18590741"
FT /id="VAR_019076"
FT VARIANT 135
FT /note="Y -> N (in F5F8D2; dbSNP:rs748641905)"
FT /evidence="ECO:0000269|PubMed:18685427"
FT /id="VAR_072246"
FT VARIANT 136
FT /note="I -> T (in F5F8D2; interferes with protein folding;
FT dbSNP:rs137852914)"
FT /evidence="ECO:0000269|PubMed:12717434,
FT ECO:0000269|PubMed:18590741"
FT /id="VAR_019077"
FT HELIX 70..78
FT /evidence="ECO:0007829|PDB:4YGB"
FT STRAND 85..89
FT /evidence="ECO:0007829|PDB:4YGB"
FT HELIX 90..97
FT /evidence="ECO:0007829|PDB:4YGB"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:2VRG"
FT HELIX 114..128
FT /evidence="ECO:0007829|PDB:4YGB"
FT STRAND 133..137
FT /evidence="ECO:0007829|PDB:4YGB"
FT HELIX 138..142
FT /evidence="ECO:0007829|PDB:4YGB"
SQ SEQUENCE 146 AA; 16390 MW; EF3F3B28E5C7A8A8 CRC64;
MTMRSLLRTP FLCGLLWAFC APGARAEEPA ASFSQPGSMG LDKNTVHDQE HIMEHLEGVI
NKPEAEMSPQ ELQLHYFKMH DYDGNNLLDG LELSTAITHV HKEEGSEQAP LMSEDELINI
IDGVLRDDDK NNDGYIDYAE FAKSLQ
