Skip Header

 
Contribute Send feedback

Reviewed, UniProtKB/Swiss-Prot P97924 (KALRN_RAT)

Last modified July 22, 2008. Version 83. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Kalirin
    EC=2.7.11.1
Alternative name(s):
    Huntingtin-associated protein-interacting protein
    Protein Duo
    Serine/threonine kinase with Dbl- and pleckstrin homology domain
    PAM COOH-terminal interactor protein 10
      Short name(s)=P-CIP10
Gene names
Name: Kalrn
Synonyms: Duo, Hapip
OrganismRattus norvegicus (Rat)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length2959 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Promotes the exchange of GDP by GTP. Activates specific Rho GTPase family members, thereby inducing various signaling mechanisms that regulate neuronal shape, growth, and plasticity, through their effects on the actin cytoskeleton. Induces lamellipodia independent of its GEF activity. Isoforms 1 and 7 are necessary for neuronal development and axonal outgrowth. Isoform 6 is required for dendritic spine formation.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Subunit structure

Interacts with the C-terminal of peptidylglycine alpha-amidating monooxygenase (PAM) and with the huntingtin-associated protein 1 (HAP1).

Subcellular location

Cytoplasm. Cytoplasmcytoskeleton. Note= Isoform 6 is largely associated with synaptosomal membranes and to punctate structures in cortical neurons. Isoforms 1 and 7 are expressed in neuronal cell bodies, isoform 7 is also found in neuronal processes.

Tissue specificity

Highly expressed in the brain and nervous system. Isoform 6 is highly enriched in the postsynaptic density fraction of the cerebral cortex.

Developmental stage

Isoforms 1 and 7 are prevelant 2 dpp, isoform 6 is not detectable until 2 weeks after birth.

Domain

The two GEF domains catalyze nucleotide exchange for RAC1 and RhoA which are bound by DH1 and DH2 respectively. The two GEF domains appear to play differing roles in neuronal development and axonal outgrowth. SH3 1 binds to the first GEF domain inhibiting GEF activity only when in the presence of a PXXP peptide, suggesting that the SH3 domain/peptide interaction mediates binding to GEF1. CRK1 SH3 domain binds to and inhibits GEF1 activity.

Post-translational modification

Autophosphorylated By similarity.

Miscellaneous

Called DUO because the encoded protein is closely related to but shorter than TRIO.

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.

Contains 1 CRAL-TRIO domain.

Contains 2 DH (DBL-homology) domains.

Contains 1 fibronectin type-III domain.

Contains 1 Ig-like C2-type (immunoglobulin-like) domain.

Contains 2 PH domains.

Contains 1 protein kinase domain.

Contains 2 SH3 domains.

Contains 5 spectrin repeats.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PamP974671EBI-1397166,EBI-1397216From a different organism.

Alternative products

This entry describes 8 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]
Isoform 1 (identifier: P97924-1)

Also known as: Kalirin-12A;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Notes: Produced by alternative splicing.
Isoform 2 (identifier: P97924-2)

Also known as: Kalirin-8B; P-CIP10B;

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MVLS → MNPPEGASEEGGAADSDVDAFFRT
     1860-1899: TLEGGSYRGS...LEEEQKAKAL → VSGHAGGSRV...HPDFVYSNCI
     1900-2959: Missing.
Notes: Produced by alternative splicing.
Isoform 3 (identifier: P97924-3)

Also known as: Kalirin-8A; P-CIP10A;

The sequence of this isoform differs from the canonical sequence as follows:
     1860-1899: TLEGGSYRGS...LEEEQKAKAL → VSGHAGGSRV...HPDFVYSNCI
     1900-2959: Missing.
Notes: Produced by alternative splicing.
Isoform 4 (identifier: P97924-4)

The sequence of this isoform differs from the canonical sequence as follows:
     923-923: E → ESLFHATSLQ
Notes: Produced by alternative splicing.
Isoform 5 (identifier: P97924-5)

Also known as: Delta Kalirin-7;

The sequence of this isoform differs from the canonical sequence as follows:
     1-623: Missing.
     1617-1636: LSGGCELTVVLQDFSAAHSS → DGNLVPRWHLGPGDPFSTYV
     1637-2959: Missing.
Notes: Produced by alternative initiation at Met-624 of isoform 6.
Isoform 6 (identifier: P97924-6)

Also known as: Kalirin-7; HAPIP;

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MVLS → MTDRFWDQWYLWYLRLLRLLDR
     1617-1636: LSGGCELTVVLQDFSAAHSS → DGNLVPRWHLGPGDPFSTYV
     1637-2959: Missing.
Notes: Produced by alternative splicing.
Isoform 7 (identifier: P97924-7)

Also known as: Kalirin-9A;

The sequence of this isoform differs from the canonical sequence as follows:
     2372-2376: KSCSW → TLLKP
     2377-2959: Missing.
Notes: Produced by alternative splicing.
Isoform 8 (identifier: P97924-8)

The sequence of this isoform differs from the canonical sequence as follows:
     705-718: DSAVSNNKTPHSSS → SAWAVIPVGNASG
     719-2959: Missing.
Notes: Produced by alternative splicing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Chain1 – 29592959Kalirin

Regions

Domain17 – 162146CRAL-TRIO
Repeat170 – 290121Spectrin 1
Repeat292 – 398107Spectrin 2
Repeat518 – 624107Spectrin 3
Repeat872 – 977106Spectrin 4
Repeat1103 – 1209107Spectrin 5
Domain1254 – 1429176DH 1
Domain1441 – 1553113PH 1
Domain1619 – 168466SH3 1
Domain1901 – 2076176DH 2
Domain2088 – 2198111PH 2
Domain2293 – 235866SH3 2
Domain2444 – 253794Ig-like C2-type
Domain2542 – 263392Fibronectin type-III
Domain2657 – 2911255Protein kinase
Nucleotide binding2663 – 26719ATP By similarity
Compositional bias664 – 6696Poly-Gln

Sites

Active site27761Proton acceptor By similarity
Binding site26861ATP By similarity

Amino acid modifications

Modified residue17231Phosphoserine By similarity
Modified residue17261Phosphoserine By similarity
Modified residue17291Phosphoserine By similarity
Modified residue17461Phosphoserine By similarity
Modified residue17721Phosphoserine By similarity
Modified residue17901Phosphoserine By similarity
Modified residue22341Phosphoserine By similarity
Disulfide bond2465 ↔ 2521 By similarity

Natural variations

Alternative sequence1 – 623623Missing in isoform 5.
Alternative sequence1 – 44MVLS → MNPPEGASEEGGAADSDVDA FFRT in isoform 2.
Alternative sequence1 – 44MVLS → MTDRFWDQWYLWYLRLLRLL DR in isoform 6.
Alternative sequence705 – 71814DSAVS…PHSSS → SAWAVIPVGNASG in isoform 8.
Alternative sequence719 – 29592241Missing in isoform 8.
Alternative sequence9231E → ESLFHATSLQ in isoform 4.
Alternative sequence1617 – 163620LSGGC…AAHSS → DGNLVPRWHLGPGDPFSTYV in isoform 5 and isoform 6.
Alternative sequence1637 – 29591323Missing in isoform 5 and isoform 6.
Alternative sequence1860 – 189940TLEGG…KAKAL → VSGHAGGSRVLPLTSMWLPG PQLGPQISYLHPDFVYSNCI in isoform 2 and isoform 3.
Alternative sequence1900 – 29591060Missing in isoform 2 and isoform 3.
Alternative sequence2372 – 23765KSCSW → TLLKP in isoform 7.
Alternative sequence2377 – 2959583Missing in isoform 7.

Experimental info

Sequence conflict461T → S in AAT39517. Ref.5
Sequence conflict621N → Y in AAT39517. Ref.5

Secondary structure

.......... 2959
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Kalirin-12A) [UniParc].

Last modified October 23, 2007. Version 3.
Checksum: 1A3C6770D1CBCC1F

FASTA2,959336,587
        10         20         30         40         50         60 
MVLSGSFRND GLKASDVLPI LKEKVAFVSG GRDKRGGPIL TFPARTNHDR IRQEDLRKLV 

        70         80         90        100        110        120 
TNLASVPSED VCKRGFTVII DMRGSKWDLI KPLLKTLQEA FPAEIHVALI IKPDNFWQKQ 

       130        140        150        160        170        180 
KTNFGSSKFI FETSMVSVEG LTKLVDPSQL TEEFDGSLDY NHEEWIELRL SLEEFFNSAV 

       190        200        210        220        230        240 
HLLSRLEDLQ EMLARKEFPV DVEGSRRLID EHTQLKKKVL KAPVEELDRE GQRLLQCIRC 

       250        260        270        280        290        300 
SDGFSGRNCI PGSADFQSLV PKITSLLDKL HSTRQHLHQM WHVRKLKLDQ CFQLRLFEQD 

       310        320        330        340        350        360 
AEKMFDWISH NKELFLQSHT EIGVSYQHAL DLQTQHNHFA MNSMNAYVNI NRIMSVASRL 

       370        380        390        400        410        420 
SEAGHYASQQ IKQISTQLDQ EWKSFAAALD ERSTILAMSA VFHQKAEQFL SGVDAWCKMC 

       430        440        450        460        470        480 
SEGGLPSEMQ DLELAIHHHQ SLYEQVTQAY TEVSQDGKAL LDVLQRPLSP GNSESLTATA 

       490        500        510        520        530        540 
NYSKAVHQVL DVVHEVLHHQ RRLESIWQHR KVRLHQRLQL CVFQQDVQQV LDWIENHGEA 

       550        560        570        580        590        600 
FLSKHTGVGK SLHRARALQK RHDDFEEVAQ NTYTNADKLL EAAEQLAQTG ECDPEEIYKA 

       610        620        630        640        650        660 
ARHLEVRIQD FVRRVEQRKL LLDMSVSFHT HTKELWTWME DLQKEVLEDV CADSVDAVQE 

       670        680        690        700        710        720 
LIKQFQQQQT ATLDATLNVI KEGEDLIQQL RSAPPSLGEP TEARDSAVSN NKTPHSSSIS 

       730        740        750        760        770        780 
HIESVLQQLD DAQVQMEELF HERKIKLDIF LQLRIFEQYT IEVTAELDAW NEDLLRQMND 

       790        800        810        820        830        840 
FNTEDLTLAE QRLQRHTERK LAMNNMTFEV IQQGQDLHQY IMEVQASGIE LICEKDVDLA 

       850        860        870        880        890        900 
AQVQELLEFL HEKQHELELN AEQTHKRLEQ CLQLRHLQAE VKQVLGWIRN GESMLNASLV 

       910        920        930        940        950        960 
NASSLSEAEQ LQREHEQFQL AIEKTHQSAL QVQQKAEALL QAGHYDADAI RECAEKVALH 

       970        980        990       1000       1010       1020 
WQQLMLKMED RLKLVNASVA FYKTSEQVCS VLESLEQEYR RDEDWCGGRD KLGPAAEMDH 

      1030       1040       1050       1060       1070       1080 
VIPLLSKHLE QKEAFLKACT LARRNAEVFL KYIHRNNVSM PSVASHTRGP EQQVKAILSE 

      1090       1100       1110       1120       1130       1140 
LLQRENRVLH FWTLKKRRLD QCQQYVVFER SAKQALDWIQ ETGEYYLSTH TSTGETTEET 

      1150       1160       1170       1180       1190       1200 
QELLKEYGEF RVPAKQTKEK VKLLIQLADS FVEKGHIHAT EIRKWVTTVD KHYRDFSLRM 

      1210       1220       1230       1240       1250       1260 
GKYRYTLEKA LGVNTEDNKD LELDIIPASL SDREVKLRDA NHEVNEEKRK SARKKEFIMA 

      1270       1280       1290       1300       1310       1320 
ELLQTEKAYV RDLHECLETY LWEMTSGVEE IPPGILNKEH IIFGNIQEIY DFHNNIFLKE 

      1330       1340       1350       1360       1370       1380 
LEKYEQLPED VGHCFVTWAD KFQMYVTYCK NKPDSNQLIL EHAGTFFDEI QQRHGLANSI 

      1390       1400       1410       1420       1430       1440 
SSYLIKPVQR VTKYQLLLKE LLTCCEEGKG ELKDGLEVML SVPKKANDAM HVSMLEGFDE 

      1450       1460       1470       1480       1490       1500 
NLDVQGELIL QDAFQVWDPK SLIRKGRERH LFLFEISLVF SKEIKDSSGH TKYVYKNKLL 

      1510       1520       1530       1540       1550       1560 
TSELGVTEHV EGDPCKFALW SGRTPSSDNK TVLKASNIET KQEWIKNIRE VIQERIIHLK 

      1570       1580       1590       1600       1610       1620 
GALKEPIQLP KTPAKLRNNS KRDGVEDGDS QGDGSSQPDT ISIASRTSQN TVESDKLSGG 

      1630       1640       1650       1660       1670       1680 
CELTVVLQDF SAAHSSELSI QVGQTVELLE RPSERPGWCL VRTTERSPPQ EGLVPSSTLC 

      1690       1700       1710       1720       1730       1740 
ISHSRSSVEM DCFFPLVKDS YSHSSGENGG KSESVANLQS QPSLNSIHSS PGPKRSTNTL 

      1750       1760       1770       1780       1790       1800 
KKWLTSPVRR LNSGKADGNI KKQKKVRDGR KSFDLGSPKP GDETTPQGDS ADEKSKKGWG 

      1810       1820       1830       1840       1850       1860 
EDEPDEESHT PLPPPMKIFD NDPTQDEMSS LLAARQAPTD VPTAADLVSA IEKLVKSKLT 

      1870       1880       1890       1900       1910       1920 
LEGGSYRGSL KDPTVCLNEG MAPPTPPRNL EEEQKAKALR GRMFVLNELV QTEKDYVKDL 

      1930       1940       1950       1960       1970       1980 
GIVVEGFMKR IEEKGVPEDM RGKEKIVFGN IHQIYDWHKD FFLAELEKCI QEQDRLAQLF 

      1990       2000       2010       2020       2030       2040 
IKHERKLHIY VWYCQNKPRS EYIVAEYDAY FEEVKQEINQ RLTLSDFLIK PIQRITKYQL 

      2050       2060       2070       2080       2090       2100 
LLKDFLRYSE KAGLECSDIE KAVELMCLVP KRCNDMMNLG RLQGFEGTLT AQGKLLQQDT 

      2110       2120       2130       2140       2150       2160 
FYVIELDAGM QSRTKERRVF LFEQIVIFSE LLRKGSLTPG YMFKRSIKMN YLVLEEDVDD 

      2170       2180       2190       2200       2210       2220 
DPCKFALMNR ETSERVILQA ANSDIQQAWV QDINQVLETQ RDFLNALQSP IEYQRKERST 

      2230       2240       2250       2260       2270       2280 
AVIRSQPPRV PQASPRPYSS VPVGSEKPPK GSSYNPPLPP LKISTSNGSP GFDYHQPGDK 

      2290       2300       2310       2320       2330       2340 
FDASKQNDLG GCNGTSTMAV IKDYYALKEN EICVSQGEVV QVLAVNQQNM CLVYQPASDH 

      2350       2360       2370       2380       2390       2400 
SPAAEGWVPG SILAPLTKAT APAESSDESI KKSCSWHTLR MRKRADVENT GKNEATGPRK 

      2410       2420       2430       2440       2450       2460 
PKDILGNKAS VKETNSSEES ECDDLDPNTS MEILNPNFIQ EVAPEFLVPL VDVTCLLGDT 

      2470       2480       2490       2500       2510       2520 
VLLQCKACGR PKPTITWKGP DQNILDTDNS SATYTISSCD SGESTLKICN LMPQDSGIYT 

      2530       2540       2550       2560       2570       2580 
CIATNDHGTA STSATVKVQG VPAAPNRPIA QERSCTSVIL RWLPPASTGN CTISGYTVEY 

      2590       2600       2610       2620       2630       2640 
REEGSQVWQQ SVASTLDTYL VIEDLSPGCP YQFRVSASNP WGISLPSEPS EFVHLPEYDA 

      2650       2660       2670       2680       2690       2700 
AADGATISWK ENFDSAYTEL NEIGRGRFSI VKKCIHKATR KDVAVKFVSK KMKKKEQAAH 

      2710       2720       2730       2740       2750       2760 
EAALLQHLQH PQYVTLHDTY ESPTSYILIL ELMDDGRLLD YLMNHDELME EKVAFYIRDI 

      2770       2780       2790       2800       2810       2820 
MEALQYLHNC RVAHLDIKPE NLLIDLRIPV PRVKLIDLED AVQISGHFHI HHLLGNPEFA 

      2830       2840       2850       2860       2870       2880 
APEVIQGIPV SLGTDIWSIG VLTYVMLSGV SPFLDESKEE TCINVCRVDF SFPHEYFCGV 

      2890       2900       2910       2920       2930       2940 
SNAARDFINV ILQEDFRRRP TAATCLQHPW LQPHNGSYSK IPLDTSRLAC FIERRKHQND 

      2950 
VRPIPNVKSY IVNRVNQGT 

« Hide

Isoform 2 (Kalirin-8B) (P-CIP10B) [UniParc].

Checksum: E4DBB818E890F453
Show »

1,919218,841
Isoform 3 (Kalirin-8A) (P-CIP10A) [UniParc].

Checksum: E3545E4CB9F59A1E
Show »

1,899216,819
Isoform 4 [UniParc].

Checksum: 6B8B3C0E9FD8CDDC
Show »

2,968337,572