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   22-FEB-2023, entry version 157.
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; 101.
DR   IntAct; Q8NHP6; 138.
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   SwissPalm; 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   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   AGR; HGNC:28381; -.
DR   CTD; 158747; -.
DR   DisGeNET; 158747; -.
DR   GeneCards; MOSPD2; -.
DR   HGNC; HGNC:28381; MOSPD2.
DR   HPA; ENSG00000130150; Tissue enhanced (brain).
DR   MIM; 301086; gene.
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; 2168468at2759; -.
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; 15 hits in 779 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:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0044232; C:organelle membrane contact site; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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; 3.40.525.10; CRAL-TRIO lipid binding domain; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 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   PANTHER; PTHR46384; MOTILE SPERM DOMAIN-CONTAINING PROTEIN 2; 1.
DR   PANTHER; PTHR46384:SF1; MOTILE SPERM DOMAIN-CONTAINING PROTEIN 2; 1.
DR   Pfam; PF00650; CRAL_TRIO; 1.
DR   Pfam; PF00635; Motile_Sperm; 1.
DR   SMART; SM00516; SEC14; 1.
DR   SUPFAM; SSF52087; CRAL/TRIO domain; 1.
DR   SUPFAM; SSF46938; CRAL/TRIO N-terminal domain; 1.
DR   SUPFAM; SSF49354; PapD-like; 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
//