MSPD2_HUMAN
ID MSPD2_HUMAN Reviewed; 518 AA.
AC Q8NHP6; Q8N3H2; Q8NA83;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Motile sperm domain-containing protein 2;
GN Name=MOSPD2;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 276-518.
RC TISSUE=Amygdala;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [5]
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=28137892; DOI=10.4049/jimmunol.1601662;
RA Mendel I., Yacov N., Salem Y., Propheta-Meiran O., Ishai E., Breitbart E.;
RT "Identification of motile sperm domain-containing protein 2 as regulator of
RT human monocyte migration.";
RL J. Immunol. 198:2125-2132(2017).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH STARD3;
RP STARD3NL; RMDN3; OSBPL1A AND CERT1, SUBCELLULAR LOCATION, DOMAIN, AND
RP MUTAGENESIS OF ARG-404; LEU-406 AND 493-TRP--SER-518.
RX PubMed=29858488; DOI=10.15252/embr.201745453;
RA Di Mattia T., Wilhelm L.P., Ikhlef S., Wendling C., Spehner D., Nomine Y.,
RA Giordano F., Mathelin C., Drin G., Tomasetto C., Alpy F.;
RT "Identification of MOSPD2, a novel scaffold for endoplasmic reticulum
RT membrane contact sites.";
RL EMBO Rep. 19:0-0(2018).
CC -!- FUNCTION: Endoplasmic reticulum-anchored receptor which modulates
CC interorganelle contacts by interacting with other organelle-bound
CC proteins via their FFAT motif (PubMed:29858488). Might have a more
CC important role in endoplasmic reticulum and endosomes contacts
CC (PubMed:29858488). Promotes migration of primary monocytes and
CC neutrophils, in response to various chemokines (PubMed:28137892).
CC {ECO:0000269|PubMed:28137892, ECO:0000269|PubMed:29858488}.
CC -!- SUBUNIT: Interacts (via MSP domain) with STARD3 (via FFAT motif),
CC STARD3NL (via FFAT motif), RMDN3 (via FFAT motif), OSBPL1A (via FFAT
CC motif) and CERT1 (via FFAT motif). {ECO:0000269|PubMed:29858488}.
CC -!- INTERACTION:
CC Q8NHP6; Q13410: BTN1A1; NbExp=3; IntAct=EBI-2812848, EBI-2372803;
CC Q8NHP6; Q9BXW6: OSBPL1A; NbExp=8; IntAct=EBI-2812848, EBI-765918;
CC Q8NHP6; Q96TC7: RMDN3; NbExp=4; IntAct=EBI-2812848, EBI-1056589;
CC Q8NHP6; Q14849: STARD3; NbExp=6; IntAct=EBI-2812848, EBI-9819324;
CC Q8NHP6; O95772: STARD3NL; NbExp=5; IntAct=EBI-2812848, EBI-3916943;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:28137892, ECO:0000269|PubMed:29858488}; Single-pass
CC type IV membrane protein {ECO:0000269|PubMed:29858488}.
CC Note=Localization to contact sites involving the endoplasmic reticulum
CC and several organelles is regulated by interaction with proteins
CC containing FFAT motif. {ECO:0000269|PubMed:29858488}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8NHP6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NHP6-2; Sequence=VSP_014046;
CC -!- TISSUE SPECIFICITY: Highly expressed in CD14(+) monocytes, and at lower
CC levels in neutrophils. Does not show significant expression in B-cells
CC or T-cells. {ECO:0000269|PubMed:28137892}.
CC -!- DOMAIN: The MSP domain is required for binding to the FFAT motif of
CC target proteins. {ECO:0000269|PubMed:29858488}.
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DR EMBL; AK093075; BAC04043.1; -; mRNA.
DR EMBL; BC030641; AAH30641.1; -; mRNA.
DR EMBL; AL834345; CAD39011.1; -; mRNA.
DR CCDS; CCDS14162.1; -. [Q8NHP6-1]
DR RefSeq; NP_001170946.1; NM_001177475.1. [Q8NHP6-2]
DR RefSeq; NP_689794.1; NM_152581.3. [Q8NHP6-1]
DR PDB; 6TQS; X-ray; 2.25 A; A/B/C/D/E/F=282-490.
DR PDB; 6TQT; X-ray; 1.50 A; A=282-490.
DR PDB; 6TQU; X-ray; 2.40 A; A/B=315-445.
DR PDBsum; 6TQS; -.
DR PDBsum; 6TQT; -.
DR PDBsum; 6TQU; -.
DR AlphaFoldDB; Q8NHP6; -.
DR SMR; Q8NHP6; -.
DR BioGRID; 127702; 98.
DR IntAct; Q8NHP6; 137.
DR MINT; Q8NHP6; -.
DR STRING; 9606.ENSP00000369860; -.
DR GlyGen; Q8NHP6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8NHP6; -.
DR PhosphoSitePlus; Q8NHP6; -.
DR BioMuta; MOSPD2; -.
DR DMDM; 67461057; -.
DR EPD; Q8NHP6; -.
DR jPOST; Q8NHP6; -.
DR MassIVE; Q8NHP6; -.
DR MaxQB; Q8NHP6; -.
DR PaxDb; Q8NHP6; -.
DR PeptideAtlas; Q8NHP6; -.
DR PRIDE; Q8NHP6; -.
DR ProteomicsDB; 73729; -. [Q8NHP6-1]
DR ProteomicsDB; 73730; -. [Q8NHP6-2]
DR Antibodypedia; 516; 79 antibodies from 16 providers.
DR DNASU; 158747; -.
DR Ensembl; ENST00000380492.8; ENSP00000369860.3; ENSG00000130150.12. [Q8NHP6-1]
DR GeneID; 158747; -.
DR KEGG; hsa:158747; -.
DR MANE-Select; ENST00000380492.8; ENSP00000369860.3; NM_152581.4; NP_689794.1.
DR UCSC; uc004cwi.4; human. [Q8NHP6-1]
DR CTD; 158747; -.
DR DisGeNET; 158747; -.
DR GeneCards; MOSPD2; -.
DR HGNC; HGNC:28381; MOSPD2.
DR HPA; ENSG00000130150; Tissue enhanced (brain).
DR neXtProt; NX_Q8NHP6; -.
DR OpenTargets; ENSG00000130150; -.
DR PharmGKB; PA134898878; -.
DR VEuPathDB; HostDB:ENSG00000130150; -.
DR eggNOG; KOG1470; Eukaryota.
DR GeneTree; ENSGT00390000016713; -.
DR HOGENOM; CLU_028924_1_0_1; -.
DR InParanoid; Q8NHP6; -.
DR OMA; YKLFWFK; -.
DR OrthoDB; 457524at2759; -.
DR PhylomeDB; Q8NHP6; -.
DR TreeFam; TF351054; -.
DR PathwayCommons; Q8NHP6; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-9013405; RHOD GTPase cycle.
DR SignaLink; Q8NHP6; -.
DR BioGRID-ORCS; 158747; 14 hits in 706 CRISPR screens.
DR ChiTaRS; MOSPD2; human.
DR GenomeRNAi; 158747; -.
DR Pharos; Q8NHP6; Tbio.
DR PRO; PR:Q8NHP6; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q8NHP6; protein.
DR Bgee; ENSG00000130150; Expressed in secondary oocyte and 181 other tissues.
DR ExpressionAtlas; Q8NHP6; baseline and differential.
DR Genevisible; Q8NHP6; HS.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0140284; C:endoplasmic reticulum-endosome membrane contact site; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0044232; C:organelle membrane contact site; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; IDA:UniProtKB.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IDA:UniProtKB.
DR CDD; cd00170; SEC14; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.40.525.10; -; 1.
DR InterPro; IPR001251; CRAL-TRIO_dom.
DR InterPro; IPR036865; CRAL-TRIO_dom_sf.
DR InterPro; IPR036273; CRAL/TRIO_N_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR000535; MSP_dom.
DR InterPro; IPR008962; PapD-like_sf.
DR Pfam; PF00650; CRAL_TRIO; 1.
DR Pfam; PF00635; Motile_Sperm; 1.
DR SMART; SM00516; SEC14; 1.
DR SUPFAM; SSF46938; SSF46938; 1.
DR SUPFAM; SSF49354; SSF49354; 1.
DR SUPFAM; SSF52087; SSF52087; 1.
DR PROSITE; PS50191; CRAL_TRIO; 1.
DR PROSITE; PS50202; MSP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chemotaxis; Endoplasmic reticulum;
KW Membrane; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..518
FT /note="Motile sperm domain-containing protein 2"
FT /id="PRO_0000213463"
FT TOPO_DOM 1..496
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 497..518
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255"
FT DOMAIN 82..239
FT /note="CRAL-TRIO"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00056"
FT DOMAIN 327..445
FT /note="MSP"
FT /evidence="ECO:0000269|PubMed:29858488"
FT REGION 252..308
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 262..281
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 282..297
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..63
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_014046"
FT VARIANT 240
FT /note="S -> N (in dbSNP:rs35164803)"
FT /id="VAR_034109"
FT MUTAGEN 404
FT /note="R->D: Prevents binding to the FFAT motif of target
FT proteins STARD3, STARD3NL, RMDN3, OSBPL1A and CERT1 and
FT impairs recruitment to interorganelle membrane contacts;
FT when associated with D-406."
FT /evidence="ECO:0000269|PubMed:29858488"
FT MUTAGEN 406
FT /note="L->D: Prevents binding to the FFAT motif of target
FT proteins STARD3, STARD3NL, RMDN3, OSBPL1A and CERT1 and
FT impairs recruitment to interorganelle membrane contacts;
FT when associated with D-404."
FT /evidence="ECO:0000269|PubMed:29858488"
FT MUTAGEN 493..518
FT /note="Missing: Loss of localization to endoplasmic
FT reticulum membrane."
FT /evidence="ECO:0000269|PubMed:29858488"
FT STRAND 326..336
FT /evidence="ECO:0007829|PDB:6TQT"
FT STRAND 346..354
FT /evidence="ECO:0007829|PDB:6TQT"
FT STRAND 356..358
FT /evidence="ECO:0007829|PDB:6TQT"
FT STRAND 360..367
FT /evidence="ECO:0007829|PDB:6TQT"
FT TURN 369..371
FT /evidence="ECO:0007829|PDB:6TQT"
FT STRAND 372..376
FT /evidence="ECO:0007829|PDB:6TQT"
FT STRAND 378..381
FT /evidence="ECO:0007829|PDB:6TQT"
FT STRAND 386..393
FT /evidence="ECO:0007829|PDB:6TQT"
FT STRAND 404..411
FT /evidence="ECO:0007829|PDB:6TQT"
FT HELIX 420..429
FT /evidence="ECO:0007829|PDB:6TQT"
FT HELIX 432..434
FT /evidence="ECO:0007829|PDB:6TQT"
FT STRAND 436..442
FT /evidence="ECO:0007829|PDB:6TQT"
SQ SEQUENCE 518 AA; 59746 MW; 6CC5920CF3B251E2 CRC64;
MAENHAQNKA KLISETRRRF EAEYVTDKSD KYDARDVERL QQDDNWVESY LSWRHNIVDE
TLKMLDESFQ WRKEISVNDL NESSIPRWLL EIGVIYLHGY DKEGNKLFWI RVKYHVKDQK
TILDKKKLIA FWLERYAKRE NGKPVTVMFD LSETGINSID MDFVRFIINC FKVYYPKYLS
KIVIFDMPWL MNAAFKIVKT WLGPEAVSLL KFTSKNEVQD YVSVEYLPPH MGGTDPFKYS
YPPLVDDDFQ TPLCENGPIT SEDETSSKED IESDGKETLE TISNEEQTPL LKKINPTEST
SKAEENEKVD SKVKAFKKPL SVFKGPLLHI SPAEELYFGS TESGEKKTLI VLTNVTKNIV
AFKVRTTAPE KYRVKPSNSS CDPGASVDIV VSPHGGLTVS AQDRFLIMAA EMEQSSGTGP
AELTQFWKEV PRNKVMEHRL RCHTVESSKP NTLTLKDNAF NMSDKTSEDI CLQLSRLLES
NRKLEDQVQR CIWFQQLLLS LTMLLLAFVT SFFYLLYS
