AB1IP_HUMAN
ID AB1IP_HUMAN Reviewed; 666 AA.
AC Q7Z5R6; Q8IWS8; Q8IYL7; Q8IZZ7;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Amyloid beta A4 precursor protein-binding family B member 1-interacting protein;
DE AltName: Full=APBB1-interacting protein 1;
DE AltName: Full=Proline-rich EVH1 ligand 1;
DE Short=PREL-1;
DE AltName: Full=Proline-rich protein 73;
DE AltName: Full=Rap1-GTP-interacting adapter molecule;
DE Short=RIAM;
DE AltName: Full=Retinoic acid-responsive proline-rich protein 1;
DE Short=RARP-1;
GN Name=APBB1IP; Synonyms=PREL1, RARP1, RIAM;
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), FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Thymus;
RX PubMed=14530287; DOI=10.1074/jbc.m308016200;
RA Inagaki T., Suzuki S., Miyamoto T., Takeda T., Yamashita K., Komatsu A.,
RA Yamauchi K., Hashizume K.;
RT "The retinoic acid-responsive proline-rich protein is identified in
RT promyeloleukemic HL-60 cells.";
RL J. Biol. Chem. 278:51685-51692(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND INTERACTION WITH RAP1A; PFN1; VASP AND ENAH.
RC TISSUE=T-cell;
RX PubMed=15469846; DOI=10.1016/j.devcel.2004.07.021;
RA Lafuente E.M., van Puijenbroek A.A., Krause M., Carman C.V., Freeman G.J.,
RA Berezovskaya A., Constantine E., Springer T.A., Gertler F.B.,
RA Boussiotis V.A.;
RT "RIAM, an Ena/VASP and profilin ligand, interacts with Rap1-GTP and
RT mediates Rap1-induced adhesion.";
RL Dev. Cell 7:585-595(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Cervix carcinoma;
RX PubMed=15642358; DOI=10.1016/j.febslet.2004.10.110;
RA Jenzora A., Behrendt B., Small J.V., Wehland J., Stradal T.E.;
RT "PREL1 provides a link from Ras signalling to the actin cytoskeleton via
RT Ena/VASP proteins.";
RL FEBS Lett. 579:455-463(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Blood;
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using sequential
RT IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55 AND SER-526, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-526, AND IDENTIFICATION BY
RP 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 [11]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-31 IN COMPLEX WITH VCL, AND
RP INTERACTION WITH VCL AND TLN1.
RX PubMed=23389036; DOI=10.1074/jbc.m112.438119;
RA Goult B.T., Zacharchenko T., Bate N., Tsang R., Hey F., Gingras A.R.,
RA Elliott P.R., Roberts G.C., Ballestrem C., Critchley D.R., Barsukov I.L.;
RT "RIAM and vinculin binding to talin are mutually exclusive and regulate
RT adhesion assembly and turnover.";
RL J. Biol. Chem. 288:8238-8249(2013).
CC -!- FUNCTION: Appears to function in the signal transduction from Ras
CC activation to actin cytoskeletal remodeling. Suppresses insulin-induced
CC promoter activities through AP1 and SRE. Mediates Rap1-induced
CC adhesion. {ECO:0000269|PubMed:14530287, ECO:0000269|PubMed:15469846}.
CC -!- SUBUNIT: Interacts, through the N-terminal Pro-rich region, with the WW
CC domain of APBB1. Interacts with RAP1A, PFN1, TLN1, VASP, VCL and ENAH.
CC {ECO:0000269|PubMed:15469846, ECO:0000269|PubMed:23389036}.
CC -!- INTERACTION:
CC Q7Z5R6; Q8IUH5: ZDHHC17; NbExp=2; IntAct=EBI-2818084, EBI-524753;
CC Q7Z5R6-2; P46379-2: BAG6; NbExp=3; IntAct=EBI-12059807, EBI-10988864;
CC Q7Z5R6-2; O43711: TLX3; NbExp=3; IntAct=EBI-12059807, EBI-3939165;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Cell projection, lamellipodium {ECO:0000250}.
CC Cell junction, focal adhesion {ECO:0000250}. Cytoplasm, cytoskeleton
CC {ECO:0000250}. Note=Colocalizes with ENA/VASP proteins at lamellipodia
CC tips and focal adhesions, and F-actin at the leading edge. At the
CC membrane surface, associates, via the PH domain, preferentially with
CC the inositol phosphates, PtdIns(5)P and PtdIns(3)P. This binding
CC appears to be necessary for the efficient interaction of the RA domain
CC to Ras-GTPases (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7Z5R6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z5R6-2; Sequence=VSP_056542, VSP_056543;
CC -!- TISSUE SPECIFICITY: Widely expressed with high expression in thymus,
CC spleen, lymph node, bone marrow and peripheral leukocytes.
CC {ECO:0000269|PubMed:14530287, ECO:0000269|PubMed:15469846}.
CC -!- INDUCTION: By all-trans-retinoic acid (ATRA).
CC -!- DOMAIN: The two Pro-rich regions are required for the suppression of
CC AP1 transcription activity.
CC -!- SIMILARITY: Belongs to the MRL family. {ECO:0000305}.
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DR EMBL; AB085852; BAC41256.1; -; mRNA.
DR EMBL; AY152730; AAN75525.1; -; mRNA.
DR EMBL; AL160287; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355798; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471072; EAW86097.1; -; Genomic_DNA.
DR EMBL; BC035636; AAH35636.1; -; mRNA.
DR EMBL; BC054516; AAH54516.1; -; mRNA.
DR CCDS; CCDS31167.1; -. [Q7Z5R6-1]
DR RefSeq; NP_061916.3; NM_019043.3. [Q7Z5R6-1]
DR RefSeq; XP_006717514.1; XM_006717451.2. [Q7Z5R6-1]
DR PDB; 2MWN; NMR; -; A=7-30.
DR PDB; 3ZDL; X-ray; 2.30 A; B=1-31.
DR PDBsum; 2MWN; -.
DR PDBsum; 3ZDL; -.
DR AlphaFoldDB; Q7Z5R6; -.
DR BMRB; Q7Z5R6; -.
DR SMR; Q7Z5R6; -.
DR BioGRID; 120012; 15.
DR CORUM; Q7Z5R6; -.
DR IntAct; Q7Z5R6; 17.
DR MINT; Q7Z5R6; -.
DR STRING; 9606.ENSP00000365411; -.
DR iPTMnet; Q7Z5R6; -.
DR PhosphoSitePlus; Q7Z5R6; -.
DR BioMuta; APBB1IP; -.
DR DMDM; 74750143; -.
DR EPD; Q7Z5R6; -.
DR jPOST; Q7Z5R6; -.
DR MassIVE; Q7Z5R6; -.
DR MaxQB; Q7Z5R6; -.
DR PaxDb; Q7Z5R6; -.
DR PeptideAtlas; Q7Z5R6; -.
DR PRIDE; Q7Z5R6; -.
DR ProteomicsDB; 69350; -. [Q7Z5R6-1]
DR ProteomicsDB; 71199; -.
DR Antibodypedia; 38122; 248 antibodies from 30 providers.
DR DNASU; 54518; -.
DR Ensembl; ENST00000356785.4; ENSP00000349237.4; ENSG00000077420.16. [Q7Z5R6-2]
DR Ensembl; ENST00000376236.9; ENSP00000365411.4; ENSG00000077420.16. [Q7Z5R6-1]
DR GeneID; 54518; -.
DR KEGG; hsa:54518; -.
DR MANE-Select; ENST00000376236.9; ENSP00000365411.4; NM_019043.4; NP_061916.3.
DR UCSC; uc001isr.4; human. [Q7Z5R6-1]
DR CTD; 54518; -.
DR DisGeNET; 54518; -.
DR GeneCards; APBB1IP; -.
DR HGNC; HGNC:17379; APBB1IP.
DR HPA; ENSG00000077420; Tissue enhanced (lymphoid).
DR MIM; 609036; gene.
DR neXtProt; NX_Q7Z5R6; -.
DR OpenTargets; ENSG00000077420; -.
DR PharmGKB; PA134933955; -.
DR VEuPathDB; HostDB:ENSG00000077420; -.
DR eggNOG; KOG3751; Eukaryota.
DR GeneTree; ENSGT00940000156105; -.
DR HOGENOM; CLU_023207_2_0_1; -.
DR InParanoid; Q7Z5R6; -.
DR OMA; QENPGHP; -.
DR OrthoDB; 786893at2759; -.
DR PhylomeDB; Q7Z5R6; -.
DR TreeFam; TF317511; -.
DR PathwayCommons; Q7Z5R6; -.
DR Reactome; R-HSA-354192; Integrin signaling.
DR Reactome; R-HSA-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins.
DR Reactome; R-HSA-372708; p130Cas linkage to MAPK signaling for integrins.
DR Reactome; R-HSA-5674135; MAP2K and MAPK activation.
DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants.
DR SignaLink; Q7Z5R6; -.
DR BioGRID-ORCS; 54518; 17 hits in 1064 CRISPR screens.
DR ChiTaRS; APBB1IP; human.
DR GeneWiki; APBB1IP; -.
DR GenomeRNAi; 54518; -.
DR Pharos; Q7Z5R6; Tbio.
DR PRO; PR:Q7Z5R6; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q7Z5R6; protein.
DR Bgee; ENSG00000077420; Expressed in blood and 171 other tissues.
DR Genevisible; Q7Z5R6; HS.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0042101; C:T cell receptor complex; IEA:Ensembl.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR GO; GO:0002291; P:T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell; IEA:Ensembl.
DR CDD; cd01259; PH_APBB1IP; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR IDEAL; IID00572; -.
DR InterPro; IPR039664; GRB/APBB1IP.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR039665; PH_APBB1IP.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000159; RA_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR11243; PTHR11243; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00788; RA; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00314; RA; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50200; RA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW Cell projection; Cytoplasm; Cytoskeleton; Membrane; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..666
FT /note="Amyloid beta A4 precursor protein-binding family B
FT member 1-interacting protein"
FT /id="PRO_0000181347"
FT DOMAIN 176..263
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 310..419
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 122..155
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 448..666
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 128..150
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 448..484
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 485..500
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 510..525
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 549..635
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 55
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 526
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 528
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8R5A3"
FT MOD_RES 531
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8R5A3"
FT VAR_SEQ 152..172
FT /note="EEEEAQAKADKIKLALEKLKE -> VSMWDQRWQDHQPLLPITDVP (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056542"
FT VAR_SEQ 173..666
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056543"
FT VARIANT 404
FT /note="T -> A (in dbSNP:rs34081356)"
FT /id="VAR_050098"
FT VARIANT 617
FT /note="A -> T (in dbSNP:rs7903226)"
FT /id="VAR_059447"
FT CONFLICT 423
FT /note="L -> F (in Ref. 1; BAC41256)"
FT /evidence="ECO:0000305"
FT CONFLICT 599
FT /note="Missing (in Ref. 2; AAN75525)"
FT /evidence="ECO:0000305"
FT HELIX 8..25
FT /evidence="ECO:0007829|PDB:3ZDL"
FT TURN 26..31
FT /evidence="ECO:0007829|PDB:3ZDL"
SQ SEQUENCE 666 AA; 73183 MW; 525C906C490D8D97 CRC64;
MGESSEDIDQ MFSTLLGEMD LLTQSLGVDT LPPPDPNPPR AEFNYSVGFK DLNESLNALE
DQDLDALMAD LVADISEAEQ RTIQAQKESL QNQHHSASLQ ASIFSGAASL GYGTNVAATG
ISQYEDDLPP PPADPVLDLP LPPPPPEPLS QEEEEAQAKA DKIKLALEKL KEAKVKKLVV
KVHMNDNSTK SLMVDERQLA RDVLDNLFEK THCDCNVDWC LYEIYPELQI ERFFEDHENV
VEVLSDWTRD TENKILFLEK EEKYAVFKNP QNFYLDNRGK KESKETNEKM NAKNKESLLE
ESFCGTSIIV PELEGALYLK EDGKKSWKRR YFLLRASGIY YVPKGKTKTS RDLACFIQFE
NVNIYYGTQH KMKYKAPTDY CFVLKHPQIQ KESQYIKYLC CDDTRTLNQW VMGIRIAKYG
KTLYDNYQRA VAKAGLASRW TNLGTVNAAA PAQPSTGPKT GTTQPNGQIP QATHSVSAVL
QEAQRHAETS KDKKPALGNH HDPAVPRAPH APKSSLPPPP PVRRSSDTSG SPATPLKAKG
TGGGGLPAPP DDFLPPPPPP PPLDDPELPP PPPDFMEPPP DFVPPPPPSY AGIAGSELPP
PPPPPPAPAP APVPDSARPP PAVAKRPPVP PKRQENPGHP GGAGGGEQDF MSDLMKALQK
KRGNVS
