ID   ARPIN_HUMAN             Reviewed;         226 AA.
AC   Q7Z6K5; E2QRD5;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2003, sequence version 1.
DT   03-AUG-2022, entry version 137.
DE   RecName: Full=Arpin;
DE   AltName: Full=Arp2/3 inhibition protein;
GN   Name=ARPIN; Synonyms=C15orf38;
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 C15ORF38-AP3S2).
RC   TISSUE=Signet-ring cell carcinoma;
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 GENOMIC DNA].
RX   PubMed=16572171; DOI=10.1038/nature04601;
RA   Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA   Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA   FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA   Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA   Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA   DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA   Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA   Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA   Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA   O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA   Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA   Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT   "Analysis of the DNA sequence and duplication history of human chromosome
RT   15.";
RL   Nature 440:671-675(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Fetal brain;
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   [4]
RP   FUNCTION, DOMAIN, INTERACTION WITH ARPC2, AND ASSOCIATION WITH THE ARP2/3
RP   COMPLEX.
RX   PubMed=24132237; DOI=10.1038/nature12611;
RA   Dang I., Gorelik R., Sousa-Blin C., Derivery E., Guerin C., Linkner J.,
RA   Nemethova M., Dumortier J.G., Giger F.A., Chipysheva T.A., Ermilova V.D.,
RA   Vacher S., Campanacci V., Herrada I., Planson A.G., Fetics S., Henriot V.,
RA   David V., Oguievetskaia K., Lakisic G., Pierre F., Steffen A., Boyreau A.,
RA   Peyrieras N., Rottner K., Zinn-Justin S., Cherfils J., Bieche I.,
RA   Alexandrova A.Y., David N.B., Small J.V., Faix J., Blanchoin L.,
RA   Gautreau A.;
RT   "Inhibitory signalling to the Arp2/3 complex steers cell migration.";
RL   Nature 503:281-284(2013).
CC   -!- FUNCTION: Regulates actin polymerization by inhibiting the actin-
CC       nucleating activity of the Arp2/3 complex; the function is competitive
CC       with nucleation promoting factors. Participates in an incoherent
CC       feedforward loop at the lamellipodium tip where it inhibits the ARP2/2
CC       complex in response to Rac signaling and where Rac also stimulates
CC       actin polymerization through the WAVE complex. Involved in steering
CC       cell migration by controlling its directional persistence.
CC       {ECO:0000269|PubMed:24132237}.
CC   -!- SUBUNIT: Associates with the Arp2/3 complex. Interacts with ARPC2;
CC       enhanced by activated RAC1. Interacts with ARPC5; the interaction is
CC       dependent on RAC1. {ECO:0000269|PubMed:24132237}.
CC   -!- INTERACTION:
CC       Q7Z6K5; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-10258086, EBI-742054;
CC       Q7Z6K5; Q9GZT8: NIF3L1; NbExp=3; IntAct=EBI-10258086, EBI-740897;
CC       Q7Z6K5; P14373: TRIM27; NbExp=3; IntAct=EBI-10258086, EBI-719493;
CC       Q7Z6K5-1; O15144: ARPC2; NbExp=2; IntAct=EBI-16079078, EBI-352356;
CC       Q7Z6K5-1; Q9H2K2: TNKS2; NbExp=5; IntAct=EBI-16079078, EBI-4398527;
CC   -!- SUBCELLULAR LOCATION: Cell projection, lamellipodium {ECO:0000250}.
CC       Note=Colocalized with the WAVE complex at lamelliupodium tip.
CC       {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q7Z6K5-1; Sequence=Displayed;
CC       Name=C15orf38-AP3S2;
CC         IsoId=Q7Z6K5-2; Sequence=VSP_047416;
CC   -!- DOMAIN: The acidic C-terminus is necessary and sufficient to inhibit
CC       ARP2/3 complex activity. {ECO:0000269|PubMed:24132237}.
CC   -!- MISCELLANEOUS: [Isoform C15orf38-AP3S2]: Based on a naturally occurring
CC       readthrough transcript which produces a C15orf38-AP3S2 fusion protein.
CC       {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the Arpin family. {ECO:0000305}.
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DR   EMBL; AK000495; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AC018988; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC027176; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC053602; AAH53602.1; -; mRNA.
DR   CCDS; CCDS42080.1; -. [Q7Z6K5-1]
DR   RefSeq; NP_001269309.1; NM_001282380.1.
DR   RefSeq; NP_872422.1; NM_182616.3. [Q7Z6K5-1]
DR   PDB; 4Z68; X-ray; 1.86 A; E=211-222.
DR   PDB; 7JPN; EM; 3.24 A; H=193-226.
DR   PDBsum; 4Z68; -.
DR   PDBsum; 7JPN; -.
DR   AlphaFoldDB; Q7Z6K5; -.
DR   SASBDB; Q7Z6K5; -.
DR   SMR; Q7Z6K5; -.
DR   BioGRID; 131507; 18.
DR   BioGRID; 1529312; 1.
DR   DIP; DIP-60587N; -.
DR   IntAct; Q7Z6K5; 10.
DR   STRING; 9606.ENSP00000350075; -.
DR   iPTMnet; Q7Z6K5; -.
DR   PhosphoSitePlus; Q7Z6K5; -.
DR   BioMuta; ARPIN; -.
DR   DMDM; 74738824; -.
DR   EPD; Q7Z6K5; -.
DR   jPOST; Q7Z6K5; -.
DR   MassIVE; Q7Z6K5; -.
DR   MaxQB; Q7Z6K5; -.
DR   PaxDb; Q7Z6K5; -.
DR   PeptideAtlas; Q7Z6K5; -.
DR   PRIDE; Q7Z6K5; -.
DR   ProteomicsDB; 15234; -.
DR   ProteomicsDB; 69435; -. [Q7Z6K5-1]
DR   TopDownProteomics; Q7Z6K5-1; -. [Q7Z6K5-1]
DR   Antibodypedia; 54707; 48 antibodies from 11 providers.
DR   DNASU; 348110; -.
DR   Ensembl; ENST00000357484.10; ENSP00000350075.5; ENSG00000242498.8. [Q7Z6K5-1]
DR   GeneID; 348110; -.
DR   KEGG; hsa:348110; -.
DR   MANE-Select; ENST00000357484.10; ENSP00000350075.5; NM_182616.4; NP_872422.1.
DR   UCSC; uc002bou.4; human. [Q7Z6K5-1]
DR   CTD; 348110; -.
DR   DisGeNET; 348110; -.
DR   GeneCards; ARPIN; -.
DR   HGNC; HGNC:28782; ARPIN.
DR   HPA; ENSG00000242498; Low tissue specificity.
DR   MIM; 615543; gene.
DR   neXtProt; NX_Q7Z6K5; -.
DR   OpenTargets; ENSG00000242498; -.
DR   PharmGKB; PA142672274; -.
DR   VEuPathDB; HostDB:ENSG00000242498; -.
DR   eggNOG; ENOG502R4IG; Eukaryota.
DR   GeneTree; ENSGT00530000064251; -.
DR   HOGENOM; CLU_106544_0_0_1; -.
DR   InParanoid; Q7Z6K5; -.
DR   OMA; WIPESEM; -.
DR   OrthoDB; 1458249at2759; -.
DR   PhylomeDB; Q7Z6K5; -.
DR   TreeFam; TF300189; -.
DR   PathwayCommons; Q7Z6K5; -.
DR   SignaLink; Q7Z6K5; -.
DR   BioGRID-ORCS; 348110; 10 hits in 1015 CRISPR screens.
DR   GenomeRNAi; 348110; -.
DR   Pharos; Q7Z6K5; Tbio.
DR   PRO; PR:Q7Z6K5; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; Q7Z6K5; protein.
DR   Bgee; ENSG00000242498; Expressed in body of pancreas and 188 other tissues.
DR   ExpressionAtlas; Q7Z6K5; baseline and differential.
DR   Genevisible; Q7Z6K5; HS.
DR   GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR   GO; GO:0033058; P:directional locomotion; IMP:UniProtKB.
DR   GO; GO:0051126; P:negative regulation of actin nucleation; IDA:UniProtKB.
DR   GO; GO:0030336; P:negative regulation of cell migration; IMP:UniProtKB.
DR   GO; GO:2000393; P:negative regulation of lamellipodium morphogenesis; IMP:UniProtKB.
DR   InterPro; IPR018889; Arpin.
DR   PANTHER; PTHR31199; PTHR31199; 1.
DR   Pfam; PF10574; UPF0552; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell projection; Reference proteome.
FT   CHAIN           1..226
FT                   /note="Arpin"
FT                   /id="PRO_0000244265"
FT   REGION          211..226
FT                   /note="Necessary and sufficient for interaction with ARPC2"
FT                   /evidence="ECO:0000269|PubMed:24132237"
FT   VAR_SEQ         225..226
FT                   /note="DD -> PEEIQQQIVRETFHLVLKRDDNICNFLEGGSLIGGSDYKLIYRHYA
FT                   TLYFVFCVDSSESELGILDLIQVFVETLDKCFENVCELDLIFHMDKVHYILQEVVMGGM
FT                   VLETNMNEIVAQIEAQNRLEKSEGGLSAAPARAVSAVKNINLPEIPRNINIGDLNIKVP
FT                   NLSQFV (in isoform C15orf38-AP3S2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_047416"
SQ   SEQUENCE   226 AA;  24943 MW;  80124CFFD6D6E455 CRC64;
     MSRIYHDGAL RNKAVQSVRL PGAWDPAAHQ GGNGVLLEGE LIDVSRHSIL DTHGRKERYY
     VLYIRPSHIH RRKFDAKGNE IEPNFSATRK VNTGFLMSSY KVEAKGDTDR LTPEALKGLV
     NKPELLALTE SLTPDHTVAF WMPESEMEVM ELELGAGVRL KTRGDGPFLD SLAKLEAGTV
     TKCNFTGDGK TGASWTDNIM AQKCSKGAAA EIREQGDGAE DEEWDD