LOCUS       NP_001346157             632 aa            linear   PRI 27-APR-2025
DEFINITION  SH2B adapter protein 2 isoform 2 [Homo sapiens].
ACCESSION   NP_001346157 XP_005277034
VERSION     NP_001346157.1
DBSOURCE    REFSEQ: accession NM_001359228.2
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 632)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   2  (residues 1 to 632)
  AUTHORS   Desbuquois,B., Carre,N. and Burnol,A.F.
  TITLE     Regulation of insulin and type 1 insulin-like growth factor
            signaling and action by the Grb10/14 and SH2B1/B2 adaptor proteins
  JOURNAL   FEBS J 280 (3), 794-816 (2013)
   PUBMED   23190452
  REMARK    GeneRIF: Studies indicate that insulin receptor (IR) and IGF Type 1
            Receptor (IGFR) have been identified as important partners of
            Grb10/14 and SH2B1/B2 adaptors.
            Review article
REFERENCE   3  (residues 1 to 632)
  AUTHORS   Davila,S., Froeling,F.E., Tan,A., Bonnard,C., Boland,G.J.,
            Snippe,H., Hibberd,M.L. and Seielstad,M.
  TITLE     New genetic associations detected in a host response study to
            hepatitis B vaccine
  JOURNAL   Genes Immun 11 (3), 232-238 (2010)
   PUBMED   20237496
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   4  (residues 1 to 632)
  AUTHORS   Gery,S., Cao,Q., Gueller,S., Xing,H., Tefferi,A. and Koeffler,H.P.
  TITLE     Lnk inhibits myeloproliferative disorder-associated JAK2 mutant,
            JAK2V617F
  JOURNAL   J Leukoc Biol 85 (6), 957-965 (2009)
   PUBMED   19293402
REFERENCE   5  (residues 1 to 632)
  AUTHORS   Ng,C., Jackson,R.A., Buschdorf,J.P., Sun,Q., Guy,G.R. and
            Sivaraman,J.
  TITLE     Structural basis for a novel intrapeptidyl H-bond and reverse
            binding of c-Cbl-TKB domain substrates
  JOURNAL   EMBO J 27 (5), 804-816 (2008)
   PUBMED   18273061
REFERENCE   6  (residues 1 to 632)
  AUTHORS   Wakioka,T., Sasaki,A., Mitsui,K., Yokouchi,M., Inoue,A., Komiya,S.
            and Yoshimura,A.
  TITLE     APS, an adaptor protein containing Pleckstrin homology (PH) and Src
            homology-2 (SH2) domains inhibits the JAK-STAT pathway in
            collaboration with c-Cbl
  JOURNAL   Leukemia 13 (5), 760-767 (1999)
   PUBMED   10374881
REFERENCE   7  (residues 1 to 632)
  AUTHORS   Moodie,S.A., Alleman-Sposeto,J. and Gustafson,T.A.
  TITLE     Identification of the APS protein as a novel insulin receptor
            substrate
  JOURNAL   J Biol Chem 274 (16), 11186-11193 (1999)
   PUBMED   10196204
REFERENCE   8  (residues 1 to 632)
  AUTHORS   Yokouchi,M., Wakioka,T., Sakamoto,H., Yasukawa,H., Ohtsuka,S.,
            Sasaki,A., Ohtsubo,M., Valius,M., Inoue,A., Komiya,S. and
            Yoshimura,A.
  TITLE     APS, an adaptor protein containing PH and SH2 domains, is
            associated with the PDGF receptor and c-Cbl and inhibits
            PDGF-induced mitogenesis
  JOURNAL   Oncogene 18 (3), 759-767 (1999)
   PUBMED   9989826
REFERENCE   9  (residues 1 to 632)
  AUTHORS   Glockner,G., Scherer,S., Schattevoy,R., Boright,A., Weber,J.,
            Tsui,L.C. and Rosenthal,A.
  TITLE     Large-scale sequencing of two regions in human chromosome 7q22:
            analysis of 650 kb of genomic sequence around the EPO and CUTL1
            loci reveals 17 genes
  JOURNAL   Genome Res 8 (10), 1060-1073 (1998)
   PUBMED   9799793
REFERENCE   10 (residues 1 to 632)
  AUTHORS   Yokouchi,M., Suzuki,R., Masuhara,M., Komiya,S., Inoue,A. and
            Yoshimura,A.
  TITLE     Cloning and characterization of APS, an adaptor molecule containing
            PH and SH2 domains that is tyrosine phosphorylated upon B-cell
            receptor stimulation
  JOURNAL   Oncogene 15 (1), 7-15 (1997)
   PUBMED   9233773
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from HY020205.1, AC091390.1,
            BI261466.1, AB000520.1 and CB053166.1.
            
            On Dec 29, 2017 this sequence version replaced XP_005277034.1.
            
            Summary: The protein encoded by this gene is expressed in B
            lymphocytes and contains pleckstrin homology and src homology 2
            (SH2) domains. In Burkitt's lymphoma cell lines, it is
            tyrosine-phosphorylated in response to B cell receptor stimulation.
            Because it binds Shc independent of stimulation and Grb2 after
            stimulation, it appears to play a role in signal transduction from
            the receptor to the Shc/Grb2 pathway. [provided by RefSeq, Jun
            2009].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1163658.237435.1,
                                           SRR1163657.85083.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA2142348
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000444095.3/ ENSP00000401883.3
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..632
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q22.1"
     Protein         1..632
                     /product="SH2B adapter protein 2 isoform 2"
                     /note="SH2 and PH domain-containing adapter protein APS;
                     adapter protein with pleckstrin homology and Src homology
                     2 domains"
                     /calculated_mol_wt=67607
     Region          22..78
                     /region_name="Phe_ZIP"
                     /note="Phenylalanine zipper; pfam08916"
                     /db_xref="CDD:462631"
     Site            52
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine.
                     /evidence=ECO:0000250|UniProtKB:Q9JID9; propagated from
                     UniProtKB/Swiss-Prot (O14492.2)"
     Site            141
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9JID9; propagated from
                     UniProtKB/Swiss-Prot (O14492.2)"
     Region          193..308
                     /region_name="PH_SH2B_family"
                     /note="SH2B adapter protein 1, 2, and 3 Pleckstrin
                     homology (PH) domain; cd01231"
                     /db_xref="CDD:269938"
     Site            310
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9JID9; propagated from
                     UniProtKB/Swiss-Prot (O14492.2)"
     Region          381..409
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (O14492.2)"
     Region          409..504
                     /region_name="SH2_SH2B2"
                     /note="Src homology 2 (SH2) domain found in SH2B adapter
                     proteins (SH2B1, SH2B2, SH2B3); cd10411"
                     /db_xref="CDD:198274"
     Site            order(424,445,466,468)
                     /site_type="other"
                     /note="phosphotyrosine binding pocket [polypeptide
                     binding]"
                     /db_xref="CDD:198274"
     Site            order(467,494)
                     /site_type="other"
                     /note="hydrophobic binding pocket [polypeptide binding]"
                     /db_xref="CDD:198274"
     Region          516..537
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (O14492.2)"
     Region          558..632
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (O14492.2)"
     Site            629
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine.
                     /evidence=ECO:0000269|PubMed:9233773; propagated from
                     UniProtKB/Swiss-Prot (O14492.2)"
     CDS             1..632
                     /gene="SH2B2"
                     /gene_synonym="APS"
                     /coded_by="NM_001359228.2:257..2155"
                     /note="isoform 2 is encoded by transcript variant 2"
                     /db_xref="CCDS:CCDS78264.2"
                     /db_xref="GeneID:10603"
                     /db_xref="HGNC:HGNC:17381"
                     /db_xref="MIM:605300"
ORIGIN      
        1 mngagpgpaa aapvpvpvpv pdwrqfcelh aqaaavdfah kfcrflrdnp aydtpdagas
       61 fsrhfaanfl dvfgeevrrv lvagpttrga avsaeamepe ladtsalkaa pyghsrssed
      121 vsthaatkar vrkgfslrnm slcvvdgvrd mwhrraspep daaaaprtae prdkwtrrlr
      181 lsrtlaakve lvdiqregal rfmvaddaaa gsggsaqwqk crlllrrava eerfrleffv
      241 ppkasrpkvs iplsaiievr ttmplempek dntfvlkven gaeyiletid slqkhswvad
      301 iqgcvdpgds eedtelsctr ggclasrvas cscelltdav dlprppetta vgavvtaphs
      361 rgrdavresl ihvpletflq tlespggsgs dsnntgeqga etdpeaepel elsdypwfhg
      421 tlsrvkaaql vlaggprnhg lfvirqsetr pgeyvltfnf qgkakhlrls lnghgqchvq
      481 hlwfqsvldm lrhfhthpip lesggsadit lrsyvraqdp ppepgptppa apaspacwsd
      541 spgqhyfssl aaaacppasp sdaagassss assssaasgp apprpvegql sarsrsnsae
      601 rlleavaata aeeppeaapg raravenqys fy
//
